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Special Issue "Antithrombin: News about an Old Molecule"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 January 2021).

Special Issue Editor

Dr. Irene Martínez-Martínez

Guest Editor
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca. Murcia, Spain
Interests: thrombosis, hemostasis, cancer, antithrombin, serpins

Special Issue Information

Dear Colleagues,

Antithrombin is a key inhibitor of the coagulation cascade. Its deficiency is associated with an increased risk of venous thrombosis and pulmonary thromboembolism. Since 1965, when O. Egeberg diagnosed antithrombin deficiency in a family with a high incidence of venous thromboembolism, knowledge about this protein has increased enormously. Although the characterization of antithrombin deficiency has helped to better understand this protein, there are several aspects that are not yet well characterized. In the last decade, some documents have demonstrated the function of antithrombin beyond hemostasis, demonstrating its function by reducing bacterial and viral infection and inhibiting some deregulated proteases in cancer. On the other hand, antithrombin is a glycoprotein and the relevance of glycosylation in its function has not always been considered. In this special issue, we welcome reviews or experimental articles that show significant advances in characterizing antithrombin function beyond inhibition of coagulation targets and those who consider the influence of glycosylation on antithrombin function.

Dr. Irene Martínez-Martínez
Guest Editor

Manuscript Submission Information

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Keywords

  • antithrombin
  • glycosylation
  • cancer
  • infection

Published Papers (2 papers)

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Research

Open AccessArticle
Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics
Int. J. Mol. Sci. 2021, 22(4), 2119; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042119 - 20 Feb 2021
Abstract
Inactivation of thrombin by the endogenous inhibitor antithrombin (AT) is a central mechanism in the regulation of hemostasis. This makes hereditary AT deficiency, which is caused by SERPINC1 gene mutations, a major thrombophilic risk factor. Aim of this study was to assess to [...] Read more.
Inactivation of thrombin by the endogenous inhibitor antithrombin (AT) is a central mechanism in the regulation of hemostasis. This makes hereditary AT deficiency, which is caused by SERPINC1 gene mutations, a major thrombophilic risk factor. Aim of this study was to assess to what extent AT mutations impair thrombin inhibition kinetics. The study population included 36 thrombophilic patients with 19 different mutations and mean AT levels of 65% in a thrombin-based functional assay, and 26 healthy controls. To assess thrombin inhibition kinetics, thrombin (3.94 mU/mL final concentration) was added to citrated plasma. Subsequently, endogenous thrombin inhibition was stopped by addition of the reversible thrombin inhibitor argatroban and the amount of argatroban-complexed thrombin quantified using an oligonucleotide-based enzyme capture assay. The plasma half-life of human thrombin was significantly longer in patients with AT mutations than in the controls (119.9 versus 55.9 s). Moreover, it was disproportionately prolonged when compared with preparations of wild type AT in plasma, in whom a comparable thrombin half-life of 120.8 s was reached at a distinctly lower AT level of 20%. These findings may help to better understand the increased thrombotic risk of SERPINC1 mutations with near normal AT plasma levels in functional assays. Full article
(This article belongs to the Special Issue Antithrombin: News about an Old Molecule)
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Open AccessArticle
Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis
Int. J. Mol. Sci. 2021, 22(1), 176; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010176 - 26 Dec 2020
Abstract
(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in [...] Read more.
(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy. Full article
(This article belongs to the Special Issue Antithrombin: News about an Old Molecule)
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